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O'Sullivan was born in Boyle, County Roscommon, Ireland, in 1911, the daughter of Mary Eva Lovatt (née Frazer)[1] and Charles Joseph O'Sullivan, an officer in the Connaught Rangers who served in World War I.[2][3] Maureen returned to Boyle in 1988 to be honoured by the town. She attended a convent school in Dublin, then the Convent of the Sacred Heart at Roehampton (now Woldingham School), England. One of her classmates there was Vivian Mary Hartley, future Academy Award-winning actress Vivien Leigh. After attending finishing school in France, O'Sullivan returned to Dublin to work with the poor. In October 1929, she sailed to New York with her mother on the British steamer R.M.S. Baltic, on the way to Hollywood to work for the Fox Film Corporation.

O'Sullivan's film career began when she met motion picture director Frank Borzage, who was doing location filming on Song o' My Heart for 20th Century Fox. He suggested she take a screen test. She did and won a part in the movie, which starred Irish tenor John McCormack. She traveled to the United States to complete the movie in Hollywood. O'Sullivan appeared in six movies at Fox, then made three more at other movie studios.

O'Sullivan's first husband was the Australian-American writer, award-winning director and Catholic convert John Villiers Farrow, from 12 September 1936 until his death on 28 January 1963. She and Farrow were the parents of seven children: Michael Damien (1939–1958), Patrick Joseph (Patrick Villiers Farrow, 1942–2009), Maria de Lourdes Villiers (Mia Farrow, b. 1945), John Charles (b. 1946),[7]Prudence Farrow (b. 1948), Stephanie Farrow (b. 1949) and Theresa Magdalena "Tisa" Farrow (b. 1951). O'Sullivan married James Cushing, a wealthy businessman, on 22 August 1983; they remained wed until her death in 1998. Maureen O'Sullivan became a US citizen on October 22, 1947 (Petition for Naturalization #133033), Los Angeles, California.[8]

Maureen O'Sullivan died in Scottsdale, Arizona, of complications from heart surgery on 23 June 1998, at age 87. O'Sullivan is buried at Most Holy Redeemer Cemetery, Niskayuna, New York, Mr. Cushing's hometown. Michael, her oldest son, was killed at age 19 in a 1958 plane crash.[11] Her son Patrick Villiers Farrow, a sculptor and peace and environmental activist, committed suicide in 2009.[12] Her grandson, Ronan Farrow, is a Pulitzer Prize-winning journalist.

O'Sullivan has a star on the Hollywood Walk of Fame at 6541 Hollywood Boulevard in Hollywood, facing the star of Johnny Weissmuller. A black plaque marks her home on Main Street in Boyle, County Roscommon, Ireland. Just around the corner from there, opposite King House, is a tree, ceremonially planted by O'Sullivan to mark her return to her birthplace.

In 1982, O'Sullivan was awarded The George Eastman Award, given by George Eastman House for distinguished contribution to the art of film.